Low concentrations of taxol cause mitotic delay followed by premature dissociation of p55CDC from Mad2 and BubR1 and abrogation of the spindle checkpoint, leading to aneuploidy

Amy E. Ikui, Chia-Ping H. Yang, Tomohiro Matsumoto, Susan Band Horwitz

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Taxol is widely used for the treatment of human cancer. Its mechanism of action in cells is dependent on drug concentration. At low concentrations of Taxol (5-10 nM), cells exhibit aberrant mitosis, including aneuploidy, in the absence of mitotic arrest. At higher concentrations of Taxol (>20 nM), the cell cycle is blocked at metaphase by spindle checkpoint activation. Here we demonstrate that low concentrations of Taxol cause mitotic delay, and result in an aneuploid population of cells after exit from mitosis. Low concentrations of Taxol dissociated p55CDC-Mad2 or p55CDC-BubR1 complexes after mitosis, whereas high concentrations of Taxol sustained the protein complex formation leading to mitotic block. The induction of apoptosis and aneuploidy by low concentrations of Taxol may result from chromosome missegregation caused by spindle checkpoint defects.

Original languageEnglish (US)
Pages (from-to)1385-1388
Number of pages4
JournalCell Cycle
Volume4
Issue number10
StatePublished - Oct 2005

Fingerprint

Aneuploidy
Paclitaxel
Mitosis
Cells
Metaphase
Chromosomes
Cell Cycle
Chemical activation
Apoptosis
Defects
Pharmaceutical Preparations
Population
Neoplasms
Proteins

Keywords

  • BubR1
  • HeLa cells
  • Mad2
  • p55CDC
  • Spindle checkpoint
  • Taxol

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

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title = "Low concentrations of taxol cause mitotic delay followed by premature dissociation of p55CDC from Mad2 and BubR1 and abrogation of the spindle checkpoint, leading to aneuploidy",
abstract = "Taxol is widely used for the treatment of human cancer. Its mechanism of action in cells is dependent on drug concentration. At low concentrations of Taxol (5-10 nM), cells exhibit aberrant mitosis, including aneuploidy, in the absence of mitotic arrest. At higher concentrations of Taxol (>20 nM), the cell cycle is blocked at metaphase by spindle checkpoint activation. Here we demonstrate that low concentrations of Taxol cause mitotic delay, and result in an aneuploid population of cells after exit from mitosis. Low concentrations of Taxol dissociated p55CDC-Mad2 or p55CDC-BubR1 complexes after mitosis, whereas high concentrations of Taxol sustained the protein complex formation leading to mitotic block. The induction of apoptosis and aneuploidy by low concentrations of Taxol may result from chromosome missegregation caused by spindle checkpoint defects.",
keywords = "BubR1, HeLa cells, Mad2, p55CDC, Spindle checkpoint, Taxol",
author = "Ikui, {Amy E.} and Yang, {Chia-Ping H.} and Tomohiro Matsumoto and {Band Horwitz}, Susan",
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journal = "Cell Cycle",
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T1 - Low concentrations of taxol cause mitotic delay followed by premature dissociation of p55CDC from Mad2 and BubR1 and abrogation of the spindle checkpoint, leading to aneuploidy

AU - Ikui, Amy E.

AU - Yang, Chia-Ping H.

AU - Matsumoto, Tomohiro

AU - Band Horwitz, Susan

PY - 2005/10

Y1 - 2005/10

N2 - Taxol is widely used for the treatment of human cancer. Its mechanism of action in cells is dependent on drug concentration. At low concentrations of Taxol (5-10 nM), cells exhibit aberrant mitosis, including aneuploidy, in the absence of mitotic arrest. At higher concentrations of Taxol (>20 nM), the cell cycle is blocked at metaphase by spindle checkpoint activation. Here we demonstrate that low concentrations of Taxol cause mitotic delay, and result in an aneuploid population of cells after exit from mitosis. Low concentrations of Taxol dissociated p55CDC-Mad2 or p55CDC-BubR1 complexes after mitosis, whereas high concentrations of Taxol sustained the protein complex formation leading to mitotic block. The induction of apoptosis and aneuploidy by low concentrations of Taxol may result from chromosome missegregation caused by spindle checkpoint defects.

AB - Taxol is widely used for the treatment of human cancer. Its mechanism of action in cells is dependent on drug concentration. At low concentrations of Taxol (5-10 nM), cells exhibit aberrant mitosis, including aneuploidy, in the absence of mitotic arrest. At higher concentrations of Taxol (>20 nM), the cell cycle is blocked at metaphase by spindle checkpoint activation. Here we demonstrate that low concentrations of Taxol cause mitotic delay, and result in an aneuploid population of cells after exit from mitosis. Low concentrations of Taxol dissociated p55CDC-Mad2 or p55CDC-BubR1 complexes after mitosis, whereas high concentrations of Taxol sustained the protein complex formation leading to mitotic block. The induction of apoptosis and aneuploidy by low concentrations of Taxol may result from chromosome missegregation caused by spindle checkpoint defects.

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